Discovery and main pharmacological properties of mibefradil (Ro 40-5967), the first selective T-type calcium channel blocker.
PROPERTIES OF MIBEFRADIL: Mibefradil is a novel calcium channel antagonist with structural and pharmacological characteristics clearly distinct from those of classical calcium antagonists. It is a potent vasodilator with a high selectivity for the coronary vasculature over the peripheral vasculature and the myocardium. Most importantly, this compound can relax vascular muscle and slow the heart rate without reducing cardiac contractility. In addition, it does not stimulate neurohormonal reflexes and it exhibits a good pharmacological profile characterized by a long duration of action.


RESULTS
The mechanism of action of mibefradil is characterized by the selective blockade of transient, low-voltage-activated (T-type) calcium channels over long-lasting, high-voltage-activated (L-type) calcium channels, which is probably responsible for many of its unique properties. CLINICAL USE OF MIBEFRADIL: Although calcium antagonists are mainly used for the treatment of hypertension and angina pectoris, there is strong preclinical evidence that mibefradil may also be beneficial in the treatment of congestive heart failure.
Clozel
J P
JP
F. Hoffmann-La Roche Ltd, Grenzacherstrasse, Basel, Switzerland.
Ertel
E A
EA
Ertel
S I
SI
D000818:Animals; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects; D020748:Mibefradil; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D013764:Tetrahydronaphthalenes; D014665:Vasodilator Agents; D020748:Mibefradil